In recent years, the use of various herbs and/or herbal medical products for the prevention of disease, alleviating the effects thereof, or for treating diseases have been gradually increasing in all societies. Throughout the human history, there have been and still are attempts for treating many diseases (diabetes, jaundice, dyspnea, etc.) by using some herbs. According to the records of the World Heath Organization (WHO), a large proportion of the world's population (70-80%) makes use of herbs for therapeutic or prophylactic purposes. Additionally, around 25% of prescription drugs in developed countries are composed of plant based active agents (vinblastine, reserpine, quinine, aspirin, etc.) (Farnsworth et al., 1985).
Particularly following the end of the 1990s, the discovery of new areas of use for medical and aromatic herbs and the increasing demand for natural products have increased the use potential thereof day by day.
Herbal medical products have long been widely used for the treatment or prophylaxis of respiratory diseases. In the treatment or prophylaxis of these diseases which are typically caused by viruses, bacteria, and/or fungi, it is quite significant both to eradicate these harmful organisms and to boost the immune system of the affected individual. This is because the immune system is comprised of processes providing protection against diseases, as well as recognizing and eliminating the pathogenic and tumor cells in a living being. The system scans the organism against any kind of foreign substances, entering or contacting the former, from viruses to parasitic worms of a wide variety, and distinguishes them from the organism's own healthy cells and tissues.
The immune system can even distinguish substances with very similar features from each other to such an extent that even proteins having a different amino acid can be distinguished from the equivalents thereof. The function of the immune system is primarily to prevent harmful foreign substances from entering the respective organism, or upon entry, to retain the substances at the place of entry, or to prevent or delay their spreading therein.
Propolis is one of the most important bee products. Besides its antibacterial, antifungal, antiviral features, a great number of beneficial biological activities such as anti-inflammatory, anti-ulcer, local anesthetic, anti-tumor and immunity stimulant properties popularizes its usage in medicine, apitherapy, health nutrition and biocosmetic fields. It comprises 150 chemical compounds, more than 20 mineral substances, beeswax, resin and pollen. In chemical terms, propolis comprises a wide variety of extremely complex and potent terpenes, benzoic acids, caffeic acids, cinnamic acids, and phenolic acids. It has a high flavonoid content.
Propolis is one of the most powerful antibiotics found in nature. It is rich in terms of amino acids and trace metals, has a very high vitamin content and contains at least 38 valuable bioflavonoids. It is an invaluable antioxidant based on its high bioflavonoid content. It was demonstrated to inactivate at least 21 bacteria species, 9 fungi species, 3 protozoa (including giardia), and a wide spectrum of viruses.
In the studies, a lot of advantages of propolis for health are demonstrated. Some of these studies are: 1) A clinical study conducted in Spain in 1988 on 138 individuals has shown that the usage of a propolis based supplement is as effective as the usage of antiprotozoal drug tinidazole which is extensively used in the treatment of infections caused by giardiasis parasite. 2) A study published in Nutrition and Cancer in 2003 has shown that propolis has revitalized apoptosis and provided the tissue decomposition of the lung cancer tumors in mouse. 3) According to National Institutes of Health, propolis may be used as an effective anti-inflammatory agent against aphtha and other gingiva wounds and peptic ulcer. 4) Blue Shield Complementary and Alternative Health has reported that propolis is two times more effective than acyclovir which is the conventional anti-viral drug in herpes treatment. 5) According to a study published in American Journal of Biochemistry and Biotechnology on February 2004, propolis kills the human breast cancer cells called MCF-7. 13% of the cancer cells of the participants were killed only within 24 hours following the administration of propolis extract.
Ginseng root is harvested after a cultivation period of 6 years and this part of the plant is used for therapeutic purposes. It comprises saponins (dammaran and oleanan derivatives; ginsenosites), polyacetylene derivatives and polysaccarides. The effects of Ginseng on the body are not local, and thus, one of the benefits of Ginseng is that it strengthens the entire body and helps in balancing entire body systems. Ginseng is an antioxidant and an important immunity system improver which increases the number of immunity system cells in the body. It is useful in the treatment of bronchitis, asthma and circulation problems. According to a study conducted by American scientists, the flu risk of people who are administered 200 mg ginseng root capsules twice a day reduced by 31%. In the laboratory and animal experiments, it is found that it is effective against prostate, stomach, kidney, liver, large intestine, brain and lung cancers. In the animals with prostate cancer, it prevented the development of cancer.
Ginger (Zingiber officinale) is also called “warming herb” and used for a long time as an important medical herb. It comprises essential oils with ether comprising Zingiberene, Zingiberol, Gingerol and Shogol. The essential oils contained which are mixed with terpenoids give the special taste and scent of ginger. The bitter substances without essential oils which make the mouth feel warm are gingerol and zingeron.
Ginger has a wide area of usage. Ginger is preventive against cancer based on stopping the Epstein-barr virus activity. 6-gingerol and 6-paradol, among the active substances of ginger, are effective in stopping promyelocytic leucaemia by disturbing the DNA synthesis. It also has anti-inflammatory effect, is effective against arthritis and headache, and is bacteriostatic. It is used against nausea, spasm and fever in kids. Based on its antiseptic effect, it is used against stomach and intestine infections and even against food poisoning. It also prevents the coagulation of the blood and has blood thinning effect. It supports the cardiovascular system by making the platelets less adherent, this in turn causes a decrease in the problems of circulation system. It is appetizing and can also be used against constipation. In addition to these, it has a warming and sedative effect in cough, flu, cold and other respiratory system diseases.
Products to be used for medical purposes have to incorporate the elements of quality, efficiency, and reliability. A product can be a “medical” product only by having these elements. In order for the product prepared from a herbal source to be used in medicine, it has to be prepared from an effective and a standardized extract, pharmacological, clinical outcomes and toxicological data thereof has to be established as well as stability of the product has to be determined. Therefore, it bears great significance to have a good stability for a product, produced from herbal sources, to be used in the treatment and prevention of diseases, or in the alleviation and/or elimination of the symptoms thereof.
Physical, chemical and microbiological factors play role in the stability of drugs or other products manufactured for medical purposes. The stability issue is not dependent on a simple cause only, but emerges as a result of many factors. Factors such as the interaction of active agents contained in a product, the interaction of excipients among themselves or with active agents, pH, light, humidity, and temperature are among many factors which may influence the stability of such products.
Until recently, the researchers deemed considerable importance on the chemical stability of pharmaceutical products rather than the physical stability thereof and conducted many studies accordingly. In many instances, however, they could show how important the changes in the physical structures of products are for the product quality, and for the durability of the technologic, microbiologic, and biopharmaceutical properties thereof. Accordingly, it was shown that primarily the physical stability of a product has to be maintained in order to sustain its quality and other features thereof, and therefore ensuring the physical stability during the development of pharmaceutical products is as important as, or sometimes more important than ensuring the chemical stability thereof.
Additionally, the physical properties taken into account in the evaluation of the physical stability of a product, particularly the taste, scent, color, clarity, uniformity, etc. of a product, also considerably influence the patient compliance. For this reason, when a novel formulation is developed, besides aiming a formulation of good physical stability, the physical properties of this formulation should be made ideal to provide high patient compliance.
Having said that, it is quite difficult to ensure the requirements mentioned above in the formulations comprising herbal agents. Due to some characteristic chemical, biological, and physical properties of herbal agents incorporated in a formulation, some difficulties are experienced in obtaining a formulation comprising such substances, and having both good physical stability and ideal features in terms of patient compliance.
The physical properties and the physical stability of a formulation are influenced directly from the characteristic properties of herbal agents contained therein. Some aspects of herbal agents contained in a formulation, such as having a bad taste, a bad scent, a bad color and similar physical properties, becoming easily oxidized, and providing a suitable medium for the reproduction of microorganisms negatively influence the physical properties and physical stability of that formulation. Additionally, in case a formulation comprises a combination of herbal agents, a correct selection of the herbal agents bears great importance, since more than one herbal agent present in the same formulation are capable to mutually affect their respective properties.
Under the light of the foregoing, it would be desirable to provide a formulation, as well as a process for the preparation of this formulation, comprising combinations of herbal agents, being capable to retain the physical stability for a long time, and having ideal physical properties in terms of patient compliance.
In detail, there is a need in the state of art to a formulation comprising Propolis extract, Ginseng root extract and Zingiber officinale extract, and having ideal physical properties to ensure high patient compliance and good physical stability, as well as to a method for preparing this formulation, which is simple, cost-efficient and time-saving.